Bottom Line:
Therefore, a simple and safe alternative is desirable.Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex.In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease.

ABSTRACTImmunoglobulin (Ig) A nephropathy (IgAN) is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit), and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit) and their subsequent immune complex formation (third hit) and glomerular deposition (fourth hit), are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with appropriate indication for treatment, and thus aid in the future development and dissemination of specific and curative treatments.

Mentions:
Specific curative treatment is required for IgAN, which is the most common form of glomerulonephritis and is associated with poor prognosis. Future research is needed to establish specific treatment regimens. However, such specific treatments may require early diagnosis of IgAN through specific targets before progression of commonly induced pathways that result in further kidney damage, such as sclerotic lesions, and an appropriate clinical trial with practical and disease-specific surrogate markers. As explained in this report, recent clinical and experimental studies emphasize that one of prospective diagnostic and disease assessment markers for IgAN are GdIgA1 and anti-glycan autoantibodies derived from the mucosa-bone marrow axis,40 and subsequent immune complexes (Figure 1). Therefore, noninvasive and real-time testing with such reasonable biomarkers on the basis of pathogenesis is critical to accomplish this goal.

Mentions:
Specific curative treatment is required for IgAN, which is the most common form of glomerulonephritis and is associated with poor prognosis. Future research is needed to establish specific treatment regimens. However, such specific treatments may require early diagnosis of IgAN through specific targets before progression of commonly induced pathways that result in further kidney damage, such as sclerotic lesions, and an appropriate clinical trial with practical and disease-specific surrogate markers. As explained in this report, recent clinical and experimental studies emphasize that one of prospective diagnostic and disease assessment markers for IgAN are GdIgA1 and anti-glycan autoantibodies derived from the mucosa-bone marrow axis,40 and subsequent immune complexes (Figure 1). Therefore, noninvasive and real-time testing with such reasonable biomarkers on the basis of pathogenesis is critical to accomplish this goal.

Bottom Line:
Therefore, a simple and safe alternative is desirable.Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex.In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease.

ABSTRACTImmunoglobulin (Ig) A nephropathy (IgAN) is the most common form of glomerular disease worldwide and is associated with a poor prognosis. Thus, development of a curative treatment and strategies for early diagnosis and treatment are urgently needed. Pathological analysis of renal biopsy is the gold standard for the diagnosis and assessment of disease activity; however, immediate and frequent assessment based on biopsy specimens is difficult. Therefore, a simple and safe alternative is desirable. On the other hand, it is now widely accepted that multi-hit steps, including production of aberrantly glycosylated serum IgA1 (first hit), and IgG or IgA autoantibodies that recognize glycan containing epitopes on glycosylated serum IgA1 (second hit) and their subsequent immune complex formation (third hit) and glomerular deposition (fourth hit), are required for continued progression of IgAN. Although the prognostic and predictive values of several markers have been discussed elsewhere, we recently developed a highly sensitive and specific diagnostic method by measuring serum levels of glycosylated serum IgA1 and related IgA immune complex. In addition, we confirmed a significant correlation between serum levels of these essential effector molecules and disease activity after treatment, suggesting that each can be considered as a practical surrogate marker of therapeutic effects in this slowly progressive disease. Such a noninvasive diagnostic and activity assessment method using these disease-oriented specific biomarkers may be useful in the early diagnosis of and intervention in IgAN, with appropriate indication for treatment, and thus aid in the future development and dissemination of specific and curative treatments.